A kind of synthetic method of carboline compounds

Abstract

The invention discloses a method for synthesizing carboline compounds, which uses pyridine derivatives to carry out coupling and reduction reactions with o-nitroaniline and its derivatives, or directly reacts with benzotriazole to convert them into heavy Nitriding the triazole intermediate, and finally reacting the obtained intermediate under the action of a reagent to obtain a substituted carbolin. Based on the improved Graebe-Ullmann method, the process optimizes the reaction raw materials, reaction reagents and conditions, and has the characteristics of enhancing the selectivity of the target product, shortening the reaction time, reducing the reaction temperature, less impurities and high yield. At the same time, the method is applicable to the synthesis of substituted α-carbolins and β-carbolins, and provides another simple and reliable selection scheme for the acquisition and utilization of such compounds.

Description

technical field [0001] The invention relates to the technical field of drug synthesis, in particular to a synthesis method of carboline compounds. Background technique [0002] Carboline, also known as carboline and diazafluorene, is a heterocyclic compound in which the pyridine ring and the pyrrole ring of indole are fused. There are currently 4 isomers, of which 2-carboline is also called α-carboline and α-carbolin, and 3-carboline is also called β-carbolin. Its natural products have anti-inflammatory, bactericidal, cytotoxic, A series of biological activities such as anticancer properties, activity of central nervous system and cardiovascular system. [0003] The synthetic route of α-carbolin has been reported in several cases. In 1924, Robinson et al first reported the improved Graebe-Ullmann method to synthesize α-carbolin, that is, o-phenylenediamine and 2-chloropyridine were heated to 140°C in ethanol and then coupled with nitrous acid in an acidic environment provi...

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Problems solved by technology

[0008] Therefore, although there are many schemes for the synthesis of α-carbolin, there are still some defects, such as low yield, expensive reagents, difficulty in preparing or obtaining starting materials, or lack of flexibility, harsh reaction conditions, etc.

However, there are few synthetic methods for β-carbolin, mainly using 1-pyridylbenzotriazole intermediates to generate target compounds under the action of ultraviolet light or zinc chloride, which is difficult to operate and highly toxic, and is inconvenient for large-scale synthesis

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